Biophysical Specializations Enrich Temporal Selectivity of MSO Neurons

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DESCRIPTION (provided by applicant): The brain performs computations using neuronal cellular and circuit properties, and sometimes encodes and decodes based on the precise timing of action potentials. Timing is important in the auditory system for various tasks, such as proper speech perception and the compelling example of sound localization involves temporal precision on the submillisecond time scale. Neurons in the auditory brain stem that form the basis for sound localization by detecting the near coincidence of interaural signals have distinctive response properties, e.g. firing only once, at stimulus onset. This property of tracking the rapidly changing aspects of a signal belies their biophysical constitution. They have a special potassium current, IK-LT, that activates below threshold, enhancing their signal-to-noise ratio, phase-locking ability and capacity for detecting coincidence of subthreshold signals, even in the presence of neural noise that comes from spontaneous activity in the auditory nerve. This project addresses systematically how the temporal processing ability of a brain stem neuron depends on IK-LT and other biophysical specializations (including other subthreshold ionic current features, the cell's dendritic architecture, where on the soma-dendritic membrane are the ionic channels for IK-LT, the effect of fast and precisely timed inhibition). Several measures of temporal integration are assessed as various pharmacological agents are used to selectively manipulate the cell's biophysical components. The research combines experimental and theoretical approaches. The experiments involve electrical recording from, individaul neurons in vitro while stimulating them directly (or via nerve bundles that converge onto them) with time-varying signals, including random components. From the theoretical side, biophysically based mathematical models will be developed that mimic and predict the neurons' behaviors. The concepts and insights develooped from this case study of auditory brain stem will be extendable to other stations in the auditory pathway and will guide the identification of biophysical mechanisms that underlie temporal selectivity and neural encoding/decoding. The ability to transmit accurately timing-related cues is important for understanding speech and a number of deficits seen in patients with auditory neuropathy. Hence this basic research relates directly to the public health issues of hearing dysfunction.